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Inter-alpha Inhibitor H4 as a Potential Biomarker Predicting the Treatment Outcomes in Patients with Hepatocellular Carcinoma

 Eun-Jung Lee  ;  Seung-Hyun Yang  ;  Kyoung-Jin Kim  ;  Hyejung Cha  ;  Seo Jin Lee  ;  Ji-Hye Kim  ;  Junkyu Song  ;  Kyung-Hee Chun  ;  Jinsil Seong 
 CANCER RESEARCH AND TREATMENT, Vol.50(3) : 646-657, 2018 
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Biomarkers ; Hepatocellular carcinoma ; ITIH4 ; Liver-directed therapy ; Prognosis
Purpose: Early prediction of treatment outcomes represents an essential step towards increased treatment efficacy and survival in patients with hepatocellular carcinoma (HCC). In this study, we performed two-dimensional electrophoresis (2-DE) followed by protein profiling to identify biomarkers predictive of therapeutic outcomes in patients with HCC who received liver-directed therapy (LDTx) involving local radiotherapy (RT), and studied the underlying mechanisms of the identified proteins. Materials and Methods: 2-DE analysis was conducted by pooling sera from patients with a good or poor prognosis; serum proteomic profiles of the two groups were compared and analyzed using matrixassisted laser desorption/ionization time-of-flight mass spectrometry. Identified proteins were confirmed via enzyme-linked immunosorbent assay. An invasion assay was performed after overexpression and knockdown of target protein in Huh7 cells. Results: Levels of inter-alpha inhibitor H4 (ITIH4), fibrinogen gamma chain, keratin 9/1 complex, carbonic anhydrase I, and carbonmonoxyhemoglobin S were changed by more than 4-fold in response to LDTx. In particular, pre-LDTx ITIH4 expression was more than 5-fold higher in patients with a good prognosis, compared to patients with a poor prognosis. The migration ability of Huh7 cells was significantly suppressed and enhanced by ITIH4 overexpression and knockdown, respectively. The tumors of patients with HCC and a good prognosis expressed high levels of ITIH4, compared to those of patients with a poor prognosis. Conclusion: Taken together, ITIH4 may be a potential therapeutic target that could inhibit cancer metastasis, as well as a prognostic marker for patients with HCC who are receiving LDTx.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
Lee, Eun Jung(이은정)
Chun, Kyung Hee(전경희) ORCID logo https://orcid.org/0000-0002-9867-7321
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